The long-range goal of this research is to purify and characterize the glucagon receptor in its guanyl nucleotide sensitive state. Using rat liver plasma membranes as the source, I propose in the next three years to (1) set up quantitative assays for measurement of the glucagon receptor after solubilization. These assays will include binding of 125I-glucagon to receptors that have been reincorporated into phospholipid vesicles and reconstitution of the receptors with plasma membranes that contain functional adenylyl cyclase systems, but are lacking in glucagon receptors to obtain a glucagon stimulable adenylyl cyclase and (2) to determine if there exist distinct guanyl-nucleotide regulatory components that modulate the glucagon receptor and adenylyl cyclase; (3) purify the glucagon receptor.